Skeletal dysplasia

Gene: LAMA5

Red List (low evidence)

Comment on list classification: There is currently only 1 family reported in literature where individuals with biallelic LAMA5 variants presented with Bent bone dysplasia syndrome. Other probands reported in literature have nephrotic syndrome and no skeletal dysplasia. Hence, this gene should remain Red on Skeletal dysplasia.

Created: 26 Oct 2026, 3 p.m. | Last Modified: 26 Oct 2026, 3:03 p.m.

Panel Version: 10.24

PMID: 33242826 Barad et al., 2020
Study identified three siblings from a single nonconsanguineous family with 'bent bone dysplasia'. Clinical findings included atrial septal defects, relative macrocephaly, micrognathia, proptosis, ear abnormalities, widely spaced nipples, elbow dislocations, and severe distal limb contractures. Significant polyhydramnios detected prenatally. Radiographic findings included distinctly bent, under-mineralized long bones, platyspondyly, hypoplastic acetabular roofs. All three affected individuals died shortly after birth. WES of the family revealed comp het LAMA5 variant c.4213G>A, p.Ala1405Thr & c.6157C>T, p.Arg2053Cys in afffected individuals. Parents and an unaffected sibling were het for one of the LAMA5 variants.
The p.Ala1405Thr variant is found at a relatively high frequency in gnomAD v4.1.2 (MAF = 0.003101 in Admixed American pop), though no homozygotes have been reported. The REVEL score is also low for this variant (Benign (Moderate) (0.08)).
Variant p.Arg2053Cys has a REVEL score of Uncertain (0.29), and MAF = 0.001837 in gnomAD (South Asian pop); 3 homozygous individuals reported.

Other case reports describe patients with biallelic LAMA5 variants manifesting in early-onset nephrotic syndrome, without skeletal dysplasia (PMIDs: 35419533;36714636;37985485).

LAMA5 association with AR LAMA5-related multisystemic syndrome has been classified as Definitive in ClinGen (Glomerulopathy GCEP, 2022). This gene is associated with AR ?Bent bone dysplasia syndrome 2, OMIM:620076 and AR Nephrotic syndrome, type 26, OMIM:620049. Resources accessed 26th Oct 2026.
Sources: Literature

Created: 26 Oct 2026, 2:53 p.m. | Last Modified: 26 Oct 2026, 2:59 p.m.

Panel Version: 10.24

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Bent bone dysplasia syndrome 2, OMIM:620076; bent bone dysplasia syndrome 2, MONDO:0859573

Publications

• 33242826